2,2-Bis(bromomethyl)propane-1,3-diol: Flame Retardant with Carcinogenic and Toxicological Concerns

2,2-Bis(bromomethyl)propane-1,3-diol is currently available with a purity of 98.5%. 2,2- Bis(bromomethyl)propane-1,3-diol was available earlier as a technical product with a purity of 79%. Several impurities were identified in the technical product: 2,2-bis(hydroxymethyl)-1bromo-3-hydroxypropane, 2,2-bis(bromomethyl)-1-bromo-3-hydroxypropane and pentaerythritol. 2,2-Bis(bromomethyl)propane-1,3-diol can be produced by replacement of the hydroxyl groups of pentaerythritol with bromide. It is a reactive flame retardant that is used primarily in unsaturated polyester resins for moulded products and in rigid polyurethane foams. It is increasingly used in CFC (chlorofluorocarbon)-free foam products designed to meet more stringent standards of flame retardancy. 2,2-Bis(bromomethyl)propane-1,3-diol may enter the environment as fugitive dust, through wastewater and through disposal of resins and foams which may contain the compound as an impurity. This substance may be persistent in water. No data were available to the Working Group on levels of 2,2-bis(bromomethyl)propane-1,3-diol in the environment.

Studies of Cancer in Experimental Animals

Oral exposure to 2,2-Bis(bromomethyl)propane-1,3-diol (BBMP), technical grade, caused tumors at several different tissue sites in rats and mice. In two-year studies, dietary administration of BBMP caused tumors of the oral cavity, esophagus, mammary gland, and thyroid gland in rats of both sexes. In male rats, it also caused mononuclear-cell leukemia and tumors of the skin, subcutaneous tissue, Zymbal gland, forestomach, small and large intestines, mesothelium, urinary bladder, lung, and seminal vesicle. In similar studies with mice, 2,2-Bis(bromomethyl)propane-1,3-diol caused tumors of the Harderian gland and lung in both sexes, the kidney in males, and the subcutaneous tissue in females (Dunnick et al. 1997; IARC 2000; NTP 1996). Dietary administration of 2,2-Bis(bromomethyl)propane-1,3-diol for three months, followed by maintenance on a control diet for up to two years, caused tumors in male rats at the same tissue sites as in the two-year study of male rats described above. However, this study found higher incidences of tumors of the oral cavity, forestomach, small and large intestines, lung, Zymbal gland, thyroid gland, and mesothelium than did the two-year study; these tumors were considered to be related to BBMP exposure.[1]

The primary routes of human exposure to 2,2-Bis(bromomethyl)propane-1,3-diol are inhalation and dermal contact. BBMP may enter the environment as dust and through wastewater. If released to air, BBMP is expected to exist in both vapor and particulate phases. The half-life of the vapor phase is estimated to be 2 days. If released to water, BBMP is expected to be adsorbed to sediments and suspended solids and not to volatilize from the surface of the water. If released to soil, it is expected to have moderate mobility, based on a soil-water partition coefficient of 420. Occupational exposure to 2,2-Bis(bromomethyl)propane-1,3-diol may occur in industries where it is used as a flame retardant, for example, in production of unsaturated polyester resins, molded products, and rigid polyurethane foam.

Reproductive and developmental effects of 2,2-Bis(bromomethyl)propane-1,3-diol

Groups of male and female Sprague-Dawley SPF-derived rats, seven to eight weeks of age, were placed on a lifetime diet supplying 0, 5 or 100 mg/kg bw per day FR-1138® (containing 80% 2,2-bis(bromomethyl)propane-1,3-diol). No changes in haematological parameters, urinary parameters or blood urea nitrogen, serum glutamic pyruvic transaminase and serum alkaline phosphatase levels were observed. Rats ingesting the dietary level of 5 mg/kg FR-1138 per day had no adverse effects related to the treatment. Treinen et al. (1989) investigated 2,2-bis(bromomethyl)propane-1,3-diol (purity, 87.3%) in a continuous breeding study by administration in the feed to Swiss CD-1 mice at levels of 0, 0.1, 0.2 and 0.4% (daily doses estimated to be 0, 141, 174 and 589 mg/kg bw, respectively) to 20 male/female pairs per group. A control group of 40 breeding pairs was included. Dosing started seven days before and continued during a 98-day cohabitation period. At the end of the 98-day cohabitation period, the males were removed, allowing the dams to deliver and rear the final litter, while dosing continued. From weaning at postnatal day 21, these F1 litters received 2,2-bis(bromomethyl)propane-1,3diol at parental doses until mated with similarly treated non-siblings at 74 ± 10 days of age (20 breeding pairs per group).[2]

Thirteen-week toxicity studies of 2,2-bis(bromomethyl)propane-1,3-diol were conducted in male and female Fischer 344/N rats and B6C3F1 mice to determine target organ toxicity. 2,2-Bis(bromomethyl)propane-1,3-diol (technical grade, 78.6% pure) was administered by gavage in corn oil for five days per week to rats, 6–7 weeks of age, at doses of 0, 50, 100, 200, 400 or 800 mg/kg bw and to mice, 6–9 weeks of age, at doses of 0, 25, 50, 100, 200 or 400 mg/kg bw, or in the feed at concentrations of 0, 1250, 2500, 5000, 10 000 or 20 000 ppm for rats and 0, 625, 1250, 2500, 5000 or 10 000 ppm for mice.Effects on the weight of male reproductive organs, epididymal spermatozoal parameters and estrous cyclicity were addressed after dietary administration of 2,2-bis(bromomethyl)propane-1,3-diol for 13 weeks to groups of 10 males and 10 females per dose level. In both studies, the kidney (papillary degeneration and necrosis) and urinary bladder (hyperplasia of the transitional-cell epithelium) were target organs, with mice being more sensitive than rats.

In conclusion, Studies on 2,2-bis(bromomethyl)propane-1,3-diol have shown that feeding rats a diet containing this substance throughout their lifetime had no adverse effects in the 5 mg/kg group. A continuous reproduction study was conducted on mice with different dose groups; a 13-week toxicity study was conducted on rats and mice, examining multiple indicators, and it was found that the kidneys and bladder were target organs, with mice being more sensitive.

References

[1]National Toxicology Program. 15th Report on Carcinogens [Internet]. Research Triangle Park (NC): National Toxicology Program; 2021 Dec 21. 2,2-Bis(bromomethyl)-1,3-propanediol (Technical Grade): CAS No. 3296-90-0.

[2]IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Some Industrial Chemicals. Lyon (FR): International Agency for Research on Cancer; 2000. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 77.) 2,2-Bis(bromomethyl)propane-1,3-diol.